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间质干细胞衍生的 II 型肺泡上皮祖细胞可减轻 LPS 诱导的急性肺损伤并降低 P63 的表达。

Mesenchymal Stem Cell-derived Type II Alveolar Epithelial Progenitor Cells Attenuate LPS-induced Acute Lung Injury and Reduce P63 Expression.

机构信息

Inflammation & Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.

Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.

出版信息

Curr Stem Cell Res Ther. 2024;19(2):245-256. doi: 10.2174/1574888X18666230501234836.

Abstract

AIM

Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a severe clinical respiratory-failure disease mainly characterized by acute damage to the alveolar epithelium and pulmonary vascular endothelial cells. Stem cell therapy has emerged as a potential regenerative strategy for ARDS/ALI, however, the outcome is limited, and the underlying mechanisms are unclear.

INTRODUCTION

We established a differentiation system for bone marrow-derived mesenchymal stem cellderived (BM-MSC) type II alveolar epithelial progenitor cells (AECIIs) and assessed their regulatory effects on lipopolysaccharide (LPS)-induced ALI.

METHODS

We induced BM-MSC differentiation into AECIIs using a specific conditioned medium. After 26 days of differentiation, 3×10 BM-MSC-AECIIs were used to treat mice with LPS-induced ALI through tracheal injection.

RESULTS

After tracheal injection, BM-MSC-AECIIs migrated to the perialveolar area and reduced LPSinduced lung inflammation and pathological injury. RNA-seq suggested that P63 protein was involved in the effects of BM-MSC-AECIIs on lung inflammation.

CONCLUSION

Our results suggest that BM-MSC-AECIIs may reduce LPS-induced acute lung injury by decreasing P63 expression.

摘要

目的

急性呼吸窘迫综合征(ARDS)/急性肺损伤(ALI)是一种严重的临床呼吸衰竭疾病,主要特征为肺泡上皮细胞和肺血管内皮细胞的急性损伤。干细胞治疗已成为 ARDS/ALI 的一种潜在的再生策略,但其疗效有限,其潜在机制尚不清楚。

简介

我们建立了骨髓间充质干细胞(BM-MSC)来源的 II 型肺泡上皮祖细胞(AECII)的分化系统,并评估了它们对脂多糖(LPS)诱导的 ALI 的调节作用。

方法

我们使用特定的条件培养基诱导 BM-MSC 分化为 AECII。分化 26 天后,通过气管内注射将 3×10 BM-MSC-AECII 用于治疗 LPS 诱导的 ALI 小鼠。

结果

气管内注射后,BM-MSC-AECII 迁移到肺泡周围区域,并减少 LPS 诱导的肺炎症和病理损伤。RNA-seq 提示 P63 蛋白参与了 BM-MSC-AECII 对肺炎症的作用。

结论

我们的结果表明,BM-MSC-AECII 可能通过降低 P63 表达来减轻 LPS 诱导的急性肺损伤。

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